Central artery pulse pressure in end-stage renal disease: the roles of aortic diameter, aortic stiffness and wave reflection.

In elderly subjects and patients with end-stage renal disease (ESRD), carotid pulse pressure (PP) is an independent and significant predictor of cardiovascular (CV) risk. Whereas in the elderly carotid diameter, but not carotid stiffness, is an associated CV risk factor, an opposite CV risk pattern was observed in ESRD patients that was associated with stiffness. Whether in ESRD patients arterial diameter, stiffness or both are involved in the mechanism(s) of increased carotid PP has never been investigated. Nondiabetic ESRD patients (n = 144) were compared with 57 control subjects matched for age, sex and mean blood pressure, but with higher brachial and carotid PP. Noninvasive echo-Doppler techniques and pulse wave velocity (PWV) and pulse wave analysis were used to evaluate cardiac and carotid arterial structures and functions using multiple stepwise regressions. In controls, carotid PP was associated only with stroke volume, arterial wave reflections and aortic PWV, but not aortic diameter. In ESRD patients, it was associated with wave reflections, aortic PWV, stroke volume and higher aortic diameter. In ESRD patients and controls, elevated carotid PP mainly reflected increased aortic PWV and earlier wave reflections. Aortic diameter had an impact only on ESRD patients, where it compensated for enhanced aortic stiffness and the more pronounced effect of reflected waves. This hemodynamic profile differs consistently from that in elderly subjects of the general population and selectively influences CV risk and drug treatment.

Cardiometabolic determinants of mortality in a geriatric population: is there a "reverse metabolic syndrome"?

AIMS: Diabetes or insulin resistance, overweight, arterial hypertension, and dyslipidaemia are recognized risk factors for cardiovascular (CV) disease. However, their predictive value and hierarchy in elderly subjects remain uncertain. METHODS: We investigated the impact of cardiometabolic risk factors on mortality in a prospective cohort study of 331 elderly high-risk subjects (mean age+/-SD: 85+/-7 years). RESULTS: Two-year total mortality was predicted by age, diabetes, low BMI, low diastolic blood pressure (DBP), low total and HDL cholesterol, and previous CV events. The effect of diabetes was explained by previous CV events. In non-diabetic subjects, mortality was predicted by high insulin sensitivity, determined by HOMA-IR and QUICKI indices. In multivariate analyses, the strongest mortality predictors were low BMI, low HDL cholesterol and previous myocardial infarction. Albumin, a marker of malnutrition, was associated with blood pressure, total and HDL cholesterol, and HOMA-IR. The inflammation marker CRP was associated with low total and HDL cholesterol, and high HOMA-IR. CONCLUSION: In very old patients, low BMI, low DBP, low total and HDL cholesterol, and high insulin sensitivity predict total mortality, indicating a "reverse metabolic syndrome" that is probably attributable to malnutrition and/or chronic disorders. These inverse associations limit the relevance of conventional risk factors. Previous CV events and HDL cholesterol remain strong predictors of mortality. Future studies should determine if and when the prevention and treatment of malnutrition in the elderly should be incorporated into conventional CV prevention.

Peripheral arterial disease and isolated systolic hypertension: the ATTEST study.

Hypertension is a risk factor for cardiovascular (CV) diseases, either coronary artery disease (CAD), peripheral artery disease (PAD) or cerebrovascular disease (CVD). The relationships between those different localizations of CV disease and the haemodynamic features of hypertension have been poorly evaluated in the past. In the ATTEST study, a geographically representative panel of 3020 general practitioners recruited 8316 consecutive patients with CV diseases (PAD, CAD or CVD, alone or in association). Blood pressure, which was not an inclusion criterion, was then measured and related to the different forms of CV diseases. Blood pressure classification involved 20% normotensive subjects, 24% subjects with controlled hypertension, 42% subjects with isolated systolic hypertension and 14% subjects with systolic-diastolic hypertension, all hypertensives with or without antihypertensive therapy. From multiple regression analysis, it appeared that subjects with systolic hypertension were characterized by the presence of PAD, with little or no presence of CAD and/or CVD. Subjects with systolic-diastolic hypertension were characterized by the presence of CAD and/or CVD, but without PAD. Although the former was only influenced by age, dyslipidaemia and diabetes mellitus influenced the latter. This study confirms the high prevalence of hypertension (80%) in a large population of patients with CV diseases selected in primary care. Analysis of different features of hypertension revealed that isolated systolic hypertension was the most prevalent form of hypertension in this treated population. Finally, one of the predominant goals of secondary prevention in subjects with PAD should be the treatment of isolated systolic hypertension.

Macro and microvasculature in hypertension: therapeutic aspects.

Macrovasculature, microvasculature and the heart determine the structure and function of the circulatory system. Due to the viscoelastic properties of large arteries, the pulsatile pressure and flow that result from intermittent ventricular ejection is smoothed out, so that microvasculature mediates the delivery of nutrients and oxygen to tissues steadily. The disruption of this function, which occurs when microvascular structure develops in response to hypertension, leads to end-organ damage. Microvascular structure is not only the site of vascular resistance, but also the origin of most of the wave reflections generating increased central systolic blood pressure (SBP) in the elderly. Nowadays many data of the literature suggest that hypertension-related damage to the micro and macrovascular system may be manageable through pharmacological agents. Among them, beta-blocking agents and diuretics poorly modify microvascular structure, whereas angiotensin and calcium entry blockade has an opposite effect, thereby reducing central wave reflections and, finally, causing a selective SBP reduction.

Structural and functional arterial properties in patients with obstructive sleep apnoea syndrome and cardiovascular comorbidities.

The increased severity of obstructive sleep apnoea syndrome (OSAS) is associated with a parallel increase in the incidence of cardiovascular events. Whether the increased severity of OSAS is in fact associated with impaired arterial properties has never been thoroughly studied. In patients with OSAS who carry a high burden of cardiovascular risk factors, we investigated whether the severity of OSAS is associated with deterioration in the arterial properties, independent of classical cardiovascular risk factors. In 74 consecutive patients with OSAS, we non-invasively assessed, by means of tonometry and high-resolution ultrasound: carotid intima-media thickness (IMT), carotid diameter and plaques, carotid-femoral pulse wave velocity (PWV), central augmentation index (AI) and central blood pressures. The respiratory disturbance index was an independent predictor of IMT and PWV but not of carotid plaques, carotid diameter, AI or central blood pressures. Several parameters of nocturnal hypoxaemia were independently correlated with carotid IMT and PWV. In conclusion, arterial stiffening and thickening are modulated by the severity of OSAS, independently from age and cardiovascular risk factors.

Insertion/deletion gene polymorphism of the angiotensin-converting enzyme and blood pressure changes in older adults. The Rotterdam study.

The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene may be involved in determining blood pressure changes. The aim of the present study was to assess the relationship between the ACE I/D gene and the change of blood pressure levels during follow-up. We calculated the difference between mean levels of SBP, DBP and PP obtained during the two observations as follows: BP mean levels obtained at third phase minus the BP mean levels at baseline and subsequently we investigated the association of the ACE I/D polymorphism and the mean changes of SBP, DBP and PP levels. The study was conducted within the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. Information on the II, ID and DD genotypes of the ACE gene and mean change of blood pressure levels were available in 3966 subjects. In adjusted models, subjects with the D allele had higher mean changes of systolic and pulse pressure (PP) than subjects with the I allele. The mean changes of systolic blood pressure were 6.1 (4.7-7.5), 8.2 (7.5-9.3) and 7.4 (5.9-8.5) mm Hg in subjects with the II, ID and DD genotype, respectively. The corresponding mean changes of PP through genotypes were 4.3 (3.3-5.4), 6.0 (5.3-6.7) and 5.9 (4.9-6.9) mm Hg, respectively. No difference was found for mean change of diastolic blood pressure among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with increased mean changes of systolic and PP.

Clinical interaction between diabetes duration and aortic stiffness in type 2 diabetes mellitus.

Diabetes complications increase with disease duration. No study was performed on the relationship between aortic stiffness and diabetes duration, taking into account the respective influence of such factors on macro- and microcirculation. In total, 618 subjects with type 2 diabetes (259 men) attending the Department of Internal Medicine of Tizi Ouzou Hospital (Algeria) were studied in collaboration with Hotel-Dieu Hospital (Paris, France). Brachial blood pressure (BP), anthropometric, clinical and biological data were evaluated. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (PWV). From lower to higher tertile of diabetes duration, age, BP and PWV (10.1±2.7 to 12.3±2.8 m s-1) increased, while diabetes control and renal function worsened (all P<0.01). Diabetes duration was independently associated with PWV (R2=0.035, P<0.0001), even after adjustment for age, BP, heart rate, cardiovascular events and metabolic syndrome. Diabetes duration was significantly correlated to the prevalence of microalbuminuria (OR (95% CL) 1.3 (1.06-1.63), P=0.01), independently of age, sex, BP and renal function. Increased aortic stiffness was independently associated with the prevalence of cardiovascular events (P<0.001), reaching its maximal value above the first 2 years of diabetes duration. In conclusion, diabetes duration is an independent determinant of aortic stiffness in subjects with type 2 diabetes, representing about 4% of PWV variability. Diabetes duration is associated with microvascular complications independently of renal function, and with macrovascular complications through the presence of increased aortic stiffness.

Association of left ventricular structural and functional abnormalities with aortic and brachial blood pressure variability in hypertensive patients: the SAFAR study.

Both brachial blood pressure (BP) level and its variability (BPV) significantly associate with left ventricular (LV) structure and function. Recent studies indicate that aortic BP is superior to brachial BP in the association with LV abnormalities. However, it remains unknown whether aortic BPV better associate with LV structural and functional abnormalities. We therefore aimed to investigate and compare aortic versus brachial BPV, in terms of the identification of LV abnormalities. Two hundred and three participants who underwent echocardiography were included in this study. Twenty-four-hour aortic and brachial ambulatory BP was measured simultaneously by a validated BP monitor (Mobil-O-Graph, Stolberg, Germany) and BPV was calculated with validated formulae. LV mass and LV diastolic dysfunction (LVDD) were evaluated by echocardiography. The prevalence of LV hypertrophy (LVH) and LVDD increased significantly with BPV indices (P⩽0.04) in trend tests. After adjustment to potential confounders, only aortic average real variability (ARV), but not brachial ARV or weighted s.d. (wSD, neither aortic nor brachial) significantly associated with LV mass index (P=0.02). Similar results were observed in logistic regression. After adjustment, only aortic ARV significantly associated with LVH (odds ratio (OR) and 95% confidence interval (CI): 2.28 (1.08, 4.82)). As for LVDD, neither the brachial nor the aortic 24-hour wSD, but the aortic and brachial ARV, associated with LVDD significantly, with OR=2.28 (95% CI: (1.03, 5.02)) and OR=2.36 (95% CI: (1.10, 5.05)), respectively. In summary, aortic BPV, especially aortic ARV, seems to be superior to brachial BPV in the association of LV structural and functional abnormalities.

Interaction between pulse wave velocity, augmentation index, pulse pressure and left ventricular function in chronic heart failure.

Pulse wave velocity (PWV), the carotid augmentation index (AIx), and pulse pressure (PP) may be prognostic factors in heart failure, but the possible influence of the ejection fraction (EF) and other simple haemodynamic variables on them has not been investigated in this setting. Noninvasive methods were used to measure carotid-radial (CR), carotid-femoral (CF) PWV and AIx, and brachial PP, in 135 consecutive patients with stable symptomatic chronic heart failure. The patients were divided into two groups, with preserved (>or=40%) or reduced (<40%) EF. CF-PWV, AIx and PP were lower in the decreased EF group (8.85+/-2.77 versus 10.60+/-2.75 m/s, P<0.001; 121+/-21 versus 132+/-24, P=0.009 and 41+/-19 versus 67+/-17 mmHg, P<0.001), but CR-PWV values were similar regardless of the EF status. These results were not modified after adjustment for age and sex. Multiple regression analysis showed that AIx and PP were systematically related to time domain parameters (heart rate or ejection duration) and EF, whatever the group. CF-PWV was weakly related to time domain values and unrelated to mean blood pressure (BP) or EF in the preserved EF group, whereas it was related to both mean BP and EF in the low EF group. In conclusion, whatever the EF level, PP and AIx were strongly modulated in the time domain, by pressure and by the EF level. The same relationships were found with CF-PWV, but only in the reduced EF group. Whether CF-PWV is the best prognostic factor in patients with 'diastolic' heart failure must be confirmed in a prospective study.

Impact of aortic stiffness on survival in end-stage renal disease.

BACKGROUND: Damage to large arteries is a major factor in the high cardiovascular morbidity and mortality of patients with end-stage renal disease (ESRD). Increased arterial stiffness and intima-media thickness, together with increased pulse pressure, are the principal arterial alterations. Whether increased aortic pulse-wave velocity (PWV), a classic marker of increased arterial stiffness, may predict all-cause and/or cardiovascular mortality has never been investigated. METHODS AND RESULTS: A cohort of 241 patients with ESRD undergoing hemodialysis was studied between April 1987 and April 1998. The mean duration of follow-up was 72+/-41 months (mean+/-SD). Mean age at entry was 51.5+/-16.3 years. Seventy-three deaths occurred, including 48 cardiovascular and 25 noncardiovascular fatal events. At entry, together with standard clinical and biochemical analyses, patients underwent echocardiography and aortic PWV measured by Doppler ultrasonography. On the basis of Cox analyses, 2 factors emerged as predictors of all-cause and cardiovascular mortality: age and aortic PWV. Hemoglobin and low diastolic pressure interfered to a smaller extent. After adjustment for all the confounding factors, an OR for PWV >12. 0 versus <9.4 m/s was 5.4 (95% CI, 2.4 to 11.9) for all-cause mortality and 5.9 (95% CI, 2.3 to 15.5) for cardiovascular mortality. For each PWV increase of 1 m/s in our study population, all-cause mortality-adjusted OR was 1.39 (95% CI, 1.19 to 1.62). CONCLUSIONS: These results provide the first direct evidence that in patients with ESRD, increased aortic stiffness determined by measurement of aortic PWV is a strong independent predictor of all-cause and mainly cardiovascular mortality.

Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure.

BACKGROUND: Aortic pulse wave velocity (PWV) is a predictor of mortality in patients with end-stage renal failure (ESRF). The PWV is partly dependent on blood pressure (BP), and a decrease in BP can attenuate the stiffness. Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated. METHODS AND RESULTS: One hundred fifty ESRF patients (aged 52+/-16 years) were monitored for 51+/-38 months. From entry until the end of follow-up, the changes of PWV in response to decreased BP were measured ultrasonographically. BP was controlled by adjustment of "dry weight" and, when necessary, with ACE inhibitors, calcium antagonists, and/or beta-blockers, in combination if necessary. Fifty-nine deaths occurred, including 40 cardiovascular and 19 noncardiovascular events. Cox analyses demonstrated that independent of BP changes, the predictors of all-cause and cardiovascular mortality were as follows: absence of PWV decrease in response to BP decrease, increased left ventricular mass, age, and preexisting cardiovascular disease. Survival was positively associated with ACE inhibitor use. After adjustment for all confounding factors, the risk ratio for the absence of PWV decrease was 2.59 (95% CI 1.51 to 4.43) for all-cause mortality and 2.35 (95% CI 1.23 to 4.41) for cardiovascular mortality. The risk ratio for ACE inhibitor use was 0.19 (95% CI 0.14 to 0.43) for all-cause mortality and 0.18 (95% CI 0.06 to 0.55) for cardiovascular mortality. CONCLUSIONS: These results indicate that in ESRF patients, the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes.

Systolic blood pressure revisited.

The clinical importance of systolic blood pressure (SBP) needs no emphasis. Its determinants are well known, but recent studies of one of these determinants, arterial distensibility, have led to results that now have clinical relevance. This review summarizes the role of arterial stiffness in ventricular-vascular coupling in the normal circulation and that disordered by aging and hypertension. The discussion defines the unfamiliar terms of compliance, distensibility and modulus and indicates how they are measured. Such measurements have increased our understanding of the parts played by the inhomogeneity of the arterial tree and reflected pressure waves in governing SBP. Elevated SBP is a recognized risk factor for cardiovascular complications among older patients, but when this elevation is due to a stiffened arterial tree, diastolic blood pressure (DBP) is necessarily reduced. Early epidemiologic studies in hypertension required a DBP > or = 90 mm Hg for hospital admission. They therefore excluded persons with high SBP, low DBP and very wide pulse pressure (PP). More recent inclusion of such patients has shown that elevation of SBP and PP is a strong predictor of cardiovascular risk. These considerations point to a possible redefinition of hypertension to include patients with lower DBP and to the inaccuracy but indispensability of the brachial artery pressure as a surrogate for aortic pressure--the pressure the heart sees. Finally, we review the known effects of available antihypertensive drugs on the arterial wall and indicate possible future directions of research stemming from wider understanding of the role of arterial distensibility in hypertension.

Should diastolic and systolic blood pressure be considered for cardiovascular risk evaluation: a study in middle-aged men and women.

OBJECTIVES: The goal of this study was to evaluate the role of diastolic blood pressure (DBP) in cardiovascular mortality for different systolic blood pressure (SBP) levels in middle-aged men and women. BACKGROUND: In middle-aged subjects it is unclear whether DBP, in addition to SBP, should be considered for risk evaluation. METHODS: Subjects (77,023 men; 48,480 women) aged 40 to 70 years old, had no major cardiovascular disease, no antihypertensive treatment and were examined at the Centre d'Investigations Preventives et Cliniques between 1972 and 1988. Mortality was assessed for an 8- to 12-year period. RESULTS: In both genders, cardiovascular mortality increased with the SBP level. In men and women with normal SBP levels, DBP did not influence cardiovascular mortality after adjustment for age and SBP. In men with systolic hypertension, a U-shaped curve relationship between cardiovascular mortality and DBP was observed, with the lowest mortality rates in the group with DBP 90 to 99 mm Hg. Compared with this group, age- and SBP-adjusted cardiovascular mortality was higher by 73% (p < 0.02) in the group with DBP <90 mm Hg and by 65% (p < 0.001) in the group with DBP > or =110 mm Hg. In women with systolic hypertension, however, DBP was positively correlated with cardiovascular mortality. CONCLUSIONS: In middle-aged subjects, classification of cardiovascular risk according to DBP levels should take into account gender, especially when SBP levels are elevated. Men with systolic hypertension are at higher risk when their DBP is "normal" than when they present a mild to moderate increase in DBP. In women of the same age, however, systolic-diastolic hypertension represents a higher risk than isolated systolic hypertension.

Influence of body height on pulsatile arterial hemodynamic data.

OBJECTIVES: This study sought to present evidence that short stature is a hemodynamic liability, which could explain in part the inverse relation between body height and cardiovascular risk. BACKGROUND: Other explanations for the association of short stature with increased cardiovascular risk include advancing age, reduced pulmonary function, genetic factors, poor childhood nutrition and small-caliber coronary arteries. This study adds another factor-the physiologic effects of reduced body height on the arterial tree, which increase left ventricular work and jeopardize myocardial perfusion. METHODS: Four hundred two subjects were studied: 149 with end-stage renal disease and 253 with normal renal function. Measurements included blood pressure, body height, cardiac cycle length, carotid to femoral artery pulse wave velocity, carotid artery pulse waves (by applanation tonometry) and the arrival time of reflected waves. Calculations included the carotid augmentation index, carotid artery compliance and the diastolic to systolic pressure-time ratio (an index of myocardial supply and demand). RESULTS: On linear and stepwise multiple regression, body height correlated with all variables except mean blood pressure. CONCLUSIONS: The early systolic arrival of reflected waves in short people in this group acts to stiffen the aorta and increase the pulsatile effort of the left ventricle, even at the same mean blood pressures. Short stature also induces a faster heart rate, which increases cardiac minute work and shorten diastole. Stiffening lowers the aortic diastolic pressure and, coupled with a shortened diastole, could adversely influence myocardial supply. Although indirect, this evidence supports a physiologic hypothesis for the body height-cardiovascular risk association.

Comparative effects of aging in men and women on the properties of the arterial tree.

OBJECTIVES: We measured the properties of the arterial tree, seeking differences between men and women as they aged. BACKGROUND: There are many differences between men and women, besides menopause, which might account for such disparities. These include body height, heart rate, stroke volume and smaller arterial diameters. Any gender differences in arterial stiffness could influence pulse pressure (PP), now recognized as a cardiovascular risk factor. METHODS: A total of 530 patients (347 men and 183 women) were classified by age into quartiles: < or = 40, 41-47, 48-54 and > or = 55 years. The middle groups represented the menopausal years. Studies included brachial artery blood pressure (BP), aortic pulse wave velocity (PWV), B-mode ultrasonography and wave form analysis of the common carotid artery (CCA), with its conversion to the aortic wave formin. Standard echocardiography provided left ventricular dimensions and flows. Calculated values included CCA compliance and distensibility, systemic compliance, stroke volume and peripheral resistance. RESULTS: At all ages, women had higher heart rates but lower BP than men. Pulse pressure, however, was lower in young women and higher in older women. Measurements influenced by body size, such as CCA diameter, compliance and systemic compliance, were lower in women. Those related to arterial wall properties, such as CCA and aortic distensibility, were the same. Although aortic PWV rose similarly with aging, PWV had more of an influence on PP in women than did mean BP. The reverse was true in men. CONCLUSIONS: Despite lower mean BP and similar arterial distensibilitvy, women develop a higher degree of pulsatility with aging, as compared with men. This is mainly due to their smaller physical characteristics, independent of the role of menopause and its related hormonal changes.

Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats.

OBJECTIVES: Because the synthesis of aldosterone is mainly modulated by angiotensin II through type I receptor stimulation and because converting enzyme inhibition (CEI) does not modify aortic extracellular matrix in old normotensive rats, the aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in old Sprague-Dawley normotensive rats. BACKGROUND: We have previously shown that long-term aldosterone antagonism prevents the age-related increase in aortic collagen accumulation in young spontaneously hypertensive rats, independent of blood pressure changes. In contrast, we reported that the positive effects of CEI in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type I receptors. METHODS: For this purpose, we studied the histomorphometric and stiffness (echo-tracking technique) changes of an eight-week treatment with the aldosterone antagonist spironolactone by comparison with placebo. RESULTS: At the end of treatment, spironolactone in conscious animals did not change intra-arterial blood pressure, aortic and carotid wall thickness, and cardiac weight. Cardiac collagen density and, to a lesser extent, carotid collagen and elastin densities and contents were significantly decreased in association with an increase of carotid distensibility. CONCLUSIONS: These results show that in old normotensive rats, spironolactone can markedly prevent cardiac and, to a lesser extent, arterial fibrosis and improve arterial stiffness, despite a lack of hypotensive effect.

Pulsatile diameter and elastic modulus of the aortic arch in essential hypertension: a noninvasive study.

A noninvasive evaluation of the aortic arch diameter was performed in 16 subjects with sustained essential hypertension and in 15 normal subjects of similar age, gender and body surface area. In all subjects, measurements were obtained of brachial mean arterial pressure and pulse pressure, cardiac mass (judged on echocardiography) and carotid-femoral pulse wave velocity together with ultrasound determinations of aortic arch diastolic and systolic diameter (suprasternal window). For each subject, pulsatile change in aortic diameter, strain and aortic arch elastic modulus were calculated. Compared with normal subjects, the hypertensive subjects showed an increase in aortic arch diameter (diastolic diameter 29.6 +/- 1.0 versus 25.4 +/- 1.0 mm, p less than 0.01), in elastic modulus (1.071 +/- 0.131 versus 0.526 +/- 0.045 10(5) N.m-2, p less than 0.001) and pulse wave velocity (11.8 +/- 0.5 versus 8.9 +/- 0.3 m/s, p less than 0.001). In the study group, a positive correlation was observed between diastolic aortic arch diameter and mean arterial pressure (r = 0.54, p less than 0.01) and between elastic modulus and cardiac mass (r = 0.60, p less than 0.01). Elastic modulus and age were positively correlated (r = 0.73, p less than 0.01) in hypertensive but not in normal subjects (r = 0.08, NS). This study is the first to demonstrate noninvasively that both the aortic arch diameter and the elastic modulus are increased in patients with sustained uncomplicated essential hypertension. These findings suggest that the increase in elastic modulus could influence the development of cardiac hypertrophy, and that both age and blood pressure act independently as factors that alter the arterial wall of subjects with sustained essential hypertension.

Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age.

Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular mortality in subjects with essential hypertension and in patients with end-stage renal disease. Its contribution to cardiovascular risk in subjects 70 to 100 years old has never been tested. A cohort of 141 subjects (mean+/-SD age, 87.1+/-6.6 years) was studied in 3 geriatrics departments in a Paris suburb. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured with a validated automatic device. During the 30-month follow-up, 56 patients died (27 from cardiovascular events). Logistic regressions indicated that age (P=0.005) and a loss of autonomy (P=0.01) were the best predictors of overall mortality. For cardiovascular mortality, aortic PWV was the major risk predictor (P=0.016). The odds ratio was 1.19 (95% confidence interval, 1.03 to 1.37). Antihypertensive drug treatment and blood pressure, including systolic and pulse pressure, had no additive role. In subjects 70 to 100 years old, aortic PWV is a strong, independent predictor of cardiovascular death, whereas systolic or pulse pressure was not. This prospective result will need to be confirmed in an intervention trial.

Arterial mechanical changes in children with familial hypercholesterolemia.

Atherosclerosis is preceded by a phase of changes in the arterial wall that could have functional consequences even before the appearance of atheromatous changes. We hypothesized that early alterations of the mechanical properties of the arterial wall could precede clinical and echographic modifications. We used an automatic, computerized, ultrasonic procedure to evaluate geometric and mechanical characteristics of the common carotid artery (CCA) in normotensive children with primary familial class IIA hypercholesterolemia (FH; n=30; mean+/-SD age, 11+/-2 years old; mean+/-SD systolic/diastolic blood pressure, 109+/-9/55+/-7 mm Hg). These subjects were compared with age-matched, nonobese control subjects (n=27; 11+/-3 years old; 112+/-10/55+/-7 mm Hg). Noninvasive ultrasonic measurements were performed by the same investigator to measure the CCA luminal systolic and diastolic diameters and intima-media thickness (IMT). The cross-sectional compliance, cross-sectional distensibility, and the incremental elastic modulus of the CCA wall were then calculated. Finally, we assessed the degree of reactive hyperemia in the brachial artery produced after distal cuff occlusion and release. The changes in brachial arterial diameter in response to reactive hyperemia (endothelium-dependent dilation) and to glyceryltrinitrate (endothelium-independent dilation) were then measured. In patients with FH, we observed a significant reduction of systodiastolic variations in diameter (by 20%, P:<0.001) without a significant difference in IMT. Cross-sectional compliance and cross-sectional distensibility were significantly reduced in FH subjects (by 15%, P:<0.05 and 19%, P:<0.01, respectively). In parallel, the incremental elastic modulus was significantly increased (by 27%, P:<0.01) in children with FH. No correlation was evident between the carotid incremental modulus and either IMT or plasma low density lipoprotein cholesterol level. There was no difference in diameter of the brachial artery at rest in control and FH subjects (3.0+/-0.5 versus 3.0+/-0.4 mm). The reactive hyperemia and glyceryltrinitrate dilation were also similar in the 2 groups. However, the flow-mediated dilation of the brachial artery was smaller in the FH subjects (4.2+/-2.9%) than in controls (9.0+/-3.1%, P:<0.001). In FH, endothelium-dependent dilation was negatively correlated with the plasma low density lipoprotein cholesterol level (P:<0.04). These results indicate that increased stiffness of the CCA wall in children with FH is independent of blood pressure and could be related to endothelial dysfunction. Thus, alterations in CCA wall mechanics could be early and easily measurable markers of atheromatous changes in the arterial wall.

Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients.

BACKGROUND: Current guidelines for the management of hypertension rest almost completely on the measurement of systolic and diastolic blood pressure. However, the arterial blood pressure wave is more correctly described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. OBJECTIVE: To explore the independent roles of pulse pressure and mean pressure as determinants of cardiovascular prognosis in older hypertensive patients. METHODS: This meta-analysis, based on individual patient data, pooled the results of the European Working Party on High Blood Pressure in the Elderly trial (n = 840), the Systolic Hypertension in Europe Trial (n = 4695), and the Systolic Hypertension in China Trial (n = 2394). The relative hazard rates associated with pulse pressure and mean pressure were calculated using Cox regression analysis, with stratification for the 3 trials and with adjustments for sex, age, previous cardiovascular complications, smoking, and treatment group. RESULTS: A 10-mm Hg wider pulse pressure increased the risk of major cardiovascular complications; after controlling for mean pressure and the other covariates, the increase in risk ranged from approximately 13% for all coronary end points (P = .02) to nearly 20% for cardiovascular mortality (P = .001). In a similar analysis, mean pressure predicted the incidence of cardiovascular complications but only after removal of pulse pressure as an explanatory variable from the model. Furthermore, the probability of a major cardiovascular end point increased with higher systolic blood pressure; at any given level of systolic blood pressure, it also increased with lower diastolic blood pressure, suggesting that the wider pulse pressure was driving the risk of major complications. CONCLUSIONS: In older hypertensive patients, pulse pressure not mean pressure is the major determinant of cardiovascular risk. The implications of these findings for the management of hypertensive patients should be further investigated in randomized controlled outcome trials in which the pulsatile component of blood pressure is differently affected by antihypertensive drug treatment.